Additional file 1 of Cathepsin D regulates cerebral Aβ42/40 ratios via differential degradation of Aβ42 and Aβ40

Additional file 1:Table S1. Determination of CatD-mediated cleavage sites within Aβ42 and Aβ40 via mass spectrometry. Table S2. Kinetics of Aβ42 vs Aβ40 degradation at pH 4.0 quantified by several independent methods. Fig. S1. The mechanism by which CatD regulates Aβ levels does not involve effects on APP, Aβ production or known Aβ-degrading proteases. Fig. S2. Soluble Aβ42 and Aβ40 levels in CatD-KO, −HET and -WT brains. Fig. S3. Cerebral Aβ levels are unchanged in another mouse model featuring profound lysosomal dysfunction and premature lethality. Fig. S4. Immunohistochemical analysis of CatD-KO mice shows selective accumulation of Aβ42 in lysosomes and other intracellular compartments by 3 weeks of age. Fig. S5. Studies in primary embryonic cultured neurons. Fig. S6. Mass spectra of Aβ42 degradation by CatD. Fig. S7. Mass spectra of Aβ40 degradation by CatD. Fig. S8. Activity of CatD against aggregated Aβ species. Fig. S9. Evidence for a statistically significant genetic association between a functional polymorphism in CTSD and risk for late-onset AD (LOAD).